The family Arenaviridae contains a single genus, Arenavirus, consisting of at least 16 currently recognized species that can be divided into Old World and New World viruses as shown in Table 1. Because of their association with individual rodent species, arenavirus species are restricted to that of their host. Rodents that have been distributed widely by humans also spread their associated virus as exemplified by the prototypic Arenavirus lymphocytic choriomeningitis virus (LCMV). LCMV is an Old World virus that is associated with the house mouse Mus domesticus and Mus musculus and is found throughout Europe and the Americas.
The most significant Arenavirus species with regards to pathogenic human infectious disease are the Old World viruses LCMV and Lassa virus (LASV) and the New World viruses Junin virus (JUNV) also known as Argentine Hemorrhagic Fever virus (AHF), Machupo virus (MACV) also known as Bolivian Hemorrhagic Fever virus (BHF), Guanarito virus (GTOV) also known as Venezuelan Hemorrhagic Fever virus (VHF), Sabia virus (SABV) and Whitewater Arroyo virus (WWAV).
LCMV is less virulent for man than the other Arenaviruses and cases usually present as a viral meningitis although deeper neurologic involvement is evident in a minority of cases, perhaps 10% or fewer in naturally observed outbreaks. Encephalitis has been diagnosed in 5% to 34% of hospitalized patients with documented LCMV. Full recovery is usual, although occasional deaths do occur (Knipe, Howley et al. 2001). A more significant risk to humans is the threat of fetal LCMV infections. It is becoming increasingly apparent that LCMV is an important cause of fetal abnormalities in the United States (Barton, Mets et al. 2002).
Lassa virus is endemic to West Africa and causes between 100,000 to 300,000 cases a year (Strauss and Strauss 2002) and the mortality of hospitalized cases is 15-20% (Knipe, Howley et al. 2001). Fatal Lassa virus infection is a relentless disease with the progression of symptoms culminating in the onset of shock and death. Clinical manifestations include aseptic meningitis, encephalitis, global encephalopathy with seizures, and more subtle neurologic problems. Lassa virus is also known to cause unusually high fetal mortality.
The New World Arenaviruses are very important disease agents that cause large outbreaks of hemorrhagic fever with high mortality rates. The number of cases is increasing with development and expanding populations that bring humans in closer association with the rodent reservoirs.
An effective attenuated virus vaccine against Junin virus (AHF) has been developed and is used widely in populations at risk of infection. However, no vaccines are in use for the other Arenaviruses. Passive immunotherapy against some Arenaviruses has shown promise but this approach is complicated due to limited availability and the need to treat with large volumes of plasma, typically two to three units.
The only existing antiviral drug used to treat infections by the viruses described above is the guanosine analog ribavarin which has shown to be moderately effective against a limited subset of the arenavirus species. Ribavarin penetrates poorly into the cerebral spinal fluid which limits its potential as an LCMV antiviral drug.
All Arenaviruses form stable, infectious aerosols and have been important causes of laboratory infections and deaths and consequently are manipulated under BSL-4 containment. The potential for many of these viruses to be used as agents of bioterrorism or biowarfare is widely accepted and as a result LCMV, JUNV, MACV, GTOV and LASV are listed as Category A Pathogens by the National Institute of Allergy and Infectious Disease (NIAID).
Thus, there remains a need for a more effective antiviral therapy against several members of the Arenaviridae family.